Frequently Asked Questions for RFA-HL-08-013: Translating Basic Behavioral and Social Science Discoveries into Interventions to Reduce Obesity: Centers for Behavioral Intervention Development (U01)

Online technical meeting for RFA HL-08-013 https://webmeeting.nih.gov/p55596797/

Q. What is the U01 (cooperative agreement) mechanism and why are these Centers being funded as U01s?

A. The U01 mechanism allows for a partnership between the NIH and the teams of researchers who will comprise the Centers funded through this RFA. Under the cooperative agreement mechanism, the NIH supports awardees' activities by working jointly with them to ensure fulfillment of programmatic goals; however, prime responsibility for the conduct of the research resides with the awardees. Given the unique and relatively novel nature of this RFA, it was thought that substantial NIH programmatic involvement and support would be important to enable successful completion of project goals.

Q. Is it intended that applicants will propose several, concurrent studies in different but related topic areas, similar to other Centers projects or to PPGs?

A. Unlike a PPG or Centers program in which researchers attempt to better understand several facets of a particular topic area, the intent of this RFA is to develop, test and refine behavioral interventions that reduce obesity or alter obesity-related behaviors. Therefore, applicants should not propose multiple studies on different topics that are conducted simultaneously (as would be expected in a PPG), but rather a series of small-scale, focused studies conducted during each of the 3 stages outlined in the RFA. The expectation is that studies will occur sequentially rather than concurrently, although in some cases, applicants may wish to propose concurrent studies – for example, if multiple intervention components are being tested.

Q: Are all 3 stages required to be included in the Research Plan?

A: Yes. Applicants must include at least one study within each of the 3 stages outlined in the RFA.

Q. The announcement does not specify a number of studies that are required. Is there a required number of studies?

A. The number of studies proposed for developing the intervention is up to the applicant, as long as at least one study is proposed in each of the 3 stages (formative/experimental for phase 1, early phase trials for phase 2, and small pilot/feasibility studies for phase 3), The number of studies can be as many as are required to develop the intervention within the budgetary constraints described in the RFA. Essentially, applicants should propose an intervention development plan & timeline that includes the number of studies needed to fully develop their proposed intervention, test its safety and efficacy, & assess its feasibility in preparation for evaluation in a Phase III clinical or community trial.

Q. Can the duration of each of the stages be different than the guidelines given in the RFA?

A. The time frames given for each stage are estimates only; applicants should use these estimates as a guide but are free to structure their timelines to include more or less time, as needed, for each of the three phases of intervention development. What is essential is that the time frames proposed for each phase are well-justified and tied to the needs and features of studies necessary to complete that phase, and congruent with the overall goal of the intervention development project being proposed.

Q: Should a Center focus on developing a single intervention (perhaps with multiple components) or several interventions?

A. This is entirely up to the applicant. Centers may choose to focus on developing a single intervention, with or without multiple components, or to develop several inter-related interventions (e.g., an applicant may develop several interventions focused on weight loss in children, aimed at separate targets such as the individual, the parents, and the school environment). Applicants may also wish to develop & to compare the performance of 2 or more different intervention approaches. Applicants are free to propose to develop and evaluate whatever intervention or configuration of interventions/intervention components they wish within the budgetary limitations outlined in the RFA.

Q. Are there requirements or constraints in terms of the targets of the interventions being developed?

A. Interventions can be targeted to the individual, family, social network, community, environmental, clinical or population level, or combinations of these, and to any age group. Depending upon the intervention(s) being developed, intervention targets and outcome measures may involve the individual (e.g., energy intake, physical activity, sedentary lifestyle, adherence to specific behavioral strategies used in weight control programs such as self-monitoring of eating and physical activity levels) or broader, aggregate outcomes (e.g., use of walking and bike paths, purchases of fruits and vegetables or other healthy foods).

Q. Can animal research be proposed as part of Stage 1?

A. Yes, Stage 1 – which involves foundational research needed to establish the basis for the intervention development work in Stages 2 and 3 -- can include research using animal models. Researchers proposing animal research in Stage 1 are advised to provide a strong rationale & justification for such studies by, for example: (1) including human experimental studies in Stage 1 which extend the animal findings to humans (2) citing evidence that translation of results from animals to humans is plausible; and (3) describing evidence that supports the link between the animal studies and the subsequent intervention development studies proposed in Stages 2 and 3.

Q. Can I propose to conduct a large-scale or Phase III trial as one of the studies in my application?

A. No, this RFA is not intended to fund large-scale, Phase III trials of obesity-reducing interventions, but rather to support early-phase intervention development research through the conduct of relatively small-scale, focused studies – experimental studies, formative research and pilot studies. The intent is to produce novel, well-characterized and feasible obesity-related interventions, based on basic behavioral and social science research findings, that are ready at the end of the 5-year project period to be evaluated for efficacy and/or effectiveness in large Phase III clinical or community trials.

Q. How is “basic behavioral and social science research” defined for purposes of this RFA?

A. The definition of basic behavioral and social science research (bBSSR) used in this FOA is very broad and involves research at the individual, small group, institution, organization, and community or population level that seeks to understand fundamental principles & processes that govern human behavior. At the individual level, this research may involve the study of behavioral factors such as cognition, memory, language, perception, personality, emotion, motivation, as well as interactions of biological, behavioral and social variables (e.g., psychophysiologic research, cognitive, affective & social neuroscience, neuroeconomics, behavioral genetics). At higher levels of aggregation, bBSSR involves the study of social variables including the structure, functions and dynamics of small groups, institutions and organizations, communities, and larger environmental, demographic, political, economic, and cultural systems. Additional details and examples of basic behavioral and social science research as used in this RFA can be found at http://obssr.od.nih.gov/about_obssr/BSSR_definition/definition.aspx

Q. How do you define “discipline” and how many different types of disciplines are required to be represented on a project team?

Q. Are applicants required to include cores, such as biostatistics, training, and management cores, in their applications, as is often the case with Centers projects?

A. Cores are not required and we do not expect applicants to propose them.

Q. Is it OK to have a virtual center, rather than have all the investigators for the Center located at the same university?

A. Yes, it's fine to have a "virtual" center spread across multiple institutions. In fact, we expect this to occur frequently, as the expertise required for the kind of transdisciplinary research solicited in this RFA is often not housed at any one institution.

Q. Can more than one group at the same university apply for this grant?

A. Yes, more than one applicant or group of applicants can apply from the same institution.

Q. Are foreign scientists and institutions eligible?

A. Yes, foreign organizations are eligible to apply. Foreign applicants should emphasize their access to or use of unusual talent, resources, or environmental conditions not readily available in the U.S. or that augment existing U.S. resources and should propose the development of interventions that are broadly applicable (i.e., generalizable to U.S. populations and settings).

Q. Is the 8% F&A cost rate only for foreign applications? Do U.S. applicants use our university’s current indirect cost rate?

A. Yes, the 8% F & A cost rate applies only to foreign applications, U.S. applicants should use their university’s current indirect cost rate.

Q: Do I need to submit the application via paper format?

A: YES. Please use the PHS 398 research grant application instructions and forms.

Q. Does the Research Center application have the same page requirements as an R01, or do U01 applications have different page requirements?

A. The page limitation for the Research Plan section of the Research Center application is the same as an R01: 25 pages or less. The RCU component of the application is limited to 5 pages.

Q. Is more than one PHS 398 form needed – one for each of the Phases/Stages defined in the RFA? Or is one PHS 398 form to be used for all stages & studies proposed?

A. Only a single PHS398 form with the standard 25 page Research Methods section is needed. The Intervention Development Timeline & descriptions of the studies to be conducted at each phase (Stages 1 - 3) should be described in one 25-page Research Methods section.

Q: Do we have to submit a proposal for a Resource & Coordination Unit (RCU)?

A: No, proposing an RCU is not mandatory. However applicants are strongly encouraged to submit an application for an RCU along with their application for research project.

Q. How do I apply for an RCU?

A. To apply for an RCU, please submit 1 application but include two sets, each consisting of a descriptive plan and budget: one for the research project (<=25 page description) and one for the Resource & Coordination Unit (<=5 page description). Include only 1 cover sheet and checklist.

Q: Do we submit a separate application for the RCU?

A: No. See above.

Q: Do we submit a separate budget for the RCU?

A: Yes, you should submit two budgets, one for the proposed research project and one for the RCU. Please see above.

Q. Is the PI of the U01 also the PI of the RCU, or can/should that be a different person?

A. Although this is up to the applicant (there is no requirement that the PI of the RCU and research center be either the same or a different person), we strongly encourage applicants to name a different individual as PI for these 2 components since the functions of each are quite different. We further suggest that a biostatistician be considered as PI of the RCU because of the potential cross-study analyses expected to be conducted.

Q. If we choose to submit RCU request along with the U01 application, it is possible to get approved for the U01 but rejected as the RCU?

A. Yes.

Q. Since NHLBI will be forming a DSMB, does that mean that the Investigator does not have to put in a DSMB in their application as would be the case in an R01?

A. That is correct. The individual research applications should not include language or budgets for DSMB members. The travel, honoraria & other expenses for DSMB members will be covered by the Resource & Coordination Unit (RCU). Research Center applicants should, however, include in their Center applications costs of PI travel to DSMB meetings to present the status of the projects. We anticipate two DSMB meetings will be held per year: at least one will be an in-person meeting to be held in the DC/Bethesda area, the second will likely be via telephone.

If you plan on submitting an application for the RCU (and we are strongly encouraging applicants to consider doing so), estimates of costs for a DSMB should be included in that budget (please budget for one in-person and one teleconference meeting per year). While you may describe the type of expertise that you believe should be included in the DSMB, please do not nominate specific members for a proposed DSMB or other advisory groups, once an RCU is selected, NHLBI will work with the RCU and the other funded applicants to generate a list of possible DSMB members, from which NHLBI will select the DSMB members.

Q. What other meeting-related travel expenses should applicants include in their budgets?

A. In addition to travel to DSMB meetings (as noted above), each awardee will be required to attend three in-person Steering Committee meetings the first year, and two in-person meetings per year thereafter. Applicants should assume for budgeting purposes that the meetings will be for two days in the Washington, DC, metro area and will require the attendance of the Principal Investigator and one other person. 

If you plan on submitting an application for the RCU, estimates of travel costs for RCU personnel to attend each of these meetings, as well as costs for securing meeting space, should be included in your RCU budget. RCU budgets should not include travel costs for CBID personnel, since these costs will be included in CBID applicants’ budgets.

Q. Does the application have to have full background, methods, statistical analysis plans, etc. for each phase of the Intervention Development plan?

A. The background should involve a coherent narrative that justifies the studies you are proposing within the three phases of research.  In terms of methods and analyses for each phase of the research, you need to provide enough detail so that reviewers can understand what you plan to do and how you plan to evaluate your progress at each step (i.e. milestones/criteria met).  If there is overlap in methodology and analysis plans, we would encourage you to find ways to streamline redundant sections so that you maximize the pages allotted for meaningful information.

Q. What is expected in terms of power calculations and sample size estimates for the formative studies, early-phase trials and pilot studies to be included in this RFA?

A. The issue of powering early phase behavioral intervention trials is complex and there is much debate about the best method(s) to use. Clearly sample size estimation for the studies involved in this RFA will require some creative approaches as standard power calculations are unlikely to be appropriate. Despite the challenges, we think it is important to consider how many subjects are needed to be able to derive meaning from the data you collect at each step. As such, power needs to be considered in concert with an estimation of criteria or milestones met. For example: To consider the intervention successful enough to proceed to the next phase of research, how many participants are needed to detect “x” magnitude of response? For formative research, you usually proceed to "saturation" point, where no new information is provided by subsequent participants. You might consider consulting a statistician familiar with early phase biomedical trials as they will likely be familiar with the existing literature about power in Phase II research. Below is a reference that may help provide an example of alternate models of sample size calculation:

Byron J. Gajewski and Matthew S. Mayo. Bayesian sample size calculations in phase II clinical trials using a mixture of informative priors. Statistics in Medicine 25.15 (2006): 2554-2566.

We know that these issues are challenging and we expect the reviewers to appreciate the challenges as well. The key is to have a well thought out plan that details how you will determine when you have the evidence to move on to the next step in the research or when you should scrap an unfruitful approach. Further, this plan should be based on existing models of power calculations/sample size estimates used in early phase research.

Q. How should I structure the budget?

Structure your budget as you would structure an R01 budget that involves multiple studies. Your business office can provide additional details regarding budgetary and grants management questions. After consulting with your business office, if additional information is needed, please contact one of the following NHLBI grants management staff:

Q. When is the Letter of Intent (LOI) due? Are LOIs required?

A. The LOI receipt date is December 16, 2008. Although LOIs are not required, the information in the LOI will assist NHLBI in planning the review and in identifying responsiveness issues at an early stage.

Q. What should be covered in the LOI?

• A. The following pieces of information will be extremely helpful for NHLBI staff in setting up the most adequate review for your application:
• Title of the proposed research
• Hypothesis/hypotheses of the proposal
• Name and contact information for the Principal Investigator
• List of anticipated key personnel and their institutions
• Number and Title of this RFA

Q. What is the budget cap? How many years can I ask for?

Q. Is this RFA expected to be reissued in 2009?

A. No, a reissuance of this RFA is not expected.